Draft guidance on co-packaged drug products: Overview

On this page

• Purpose
• Scope and application
• Policy objectives
• Background
• Types of co-packaged products: Drug kits and convenience packs
• Establishment and site licensing requirements
• Post-market reporting requirements
• Post-market safety and recalls
• Note about guidance documents in general

Purpose

This draft guidance outlines the regulatory requirements for co-packaged drug products and their components, in accordance with the Food and Drugs Act and the:

• Food and Drug Regulations (FDR)
• Medical Devices Regulations (MDR)
• Natural Health Products Regulations (NHPR)

Co-packaged drug products are made up of 2 or more components sold together in a single package, at least 1 of which is a prescription or non-prescription pharmaceutical or biologic drug subject to the FDR. Co-packaged drug products are available in many formats, including those made up of a drug component together with:

• other health products (other drugs, medical devices or natural health products)
• cosmetics or other consumer products

This guidance:

• defines types of co-packaged products, where at least 1 component is a pharmaceutical or biologic drug (co-packaged drug product)
• clarifies the circumstances under which a drug identification number (DIN) must be assigned to a co-packaged drug product before it may be marketed
• clarifies packaging, labelling, importation and distribution requirements for products intended to be sold as co-packaged drug products in Canada
• clarifies the circumstances under which other authorizations may be required for a co-packaged drug product before it may be marketed
• clarifies requirements for third-party packagers and labellers of certain co-packaged products such as convenience packs

Once finalized and implemented, this draft guidance will replace the Health Canada policy on assigning drug identification numbers for drug products in kits.

Scope and application

Note about terminology

For the purposes of this guidance and in the context of a co-packaged drug product:

• “drug component” refers to prescription or non-prescription pharmaceuticals and biologic drugs for human use regulated under the FDR, including through the assignment of a DIN
• “other components” refers to other products (for instance, natural health products, medical devices, cosmetics and consumer products) that:
  • are regulated under separate schemes and
  • may have their own unique product identification numbers, such as natural product numbers (NPN), DIN-HM for homeopathic medicines and medical device identifiers associated with the name of the device

Scope

This guidance applies to co-packaged drug products for human use intended to be marketed in Canada by authorized sources, such as licensed distributors, importers or wholesalers.

All health products that are included in a package together with a drug component
must comply with all regulations that apply to the health product. An example would be licensing and labelling requirements.

This guidance is relevant to the following stakeholders:

• holders of authorizations for co-packaged drug products or drug components
• third parties involved in packaging, labelling or selling co-packaged drug products
• importers of a drug (intended to be imported into Canada) that may apply for a DIN
• manufacturers, importers and distributors of all classes of medical devices included in a co-packaged drug product

This guidance does not apply to the following types of products, as other policies may apply:

• co-packaged products containing medical devices and natural health products without a drug component
• fixed-dose combination drugs:
  • 2 or more drugs combined into a single dosage form without co-packaging
• drug-medical device combination products:
  • therapeutic products that combine at least 1 drug component and at least 1 device component (which by themselves would be classified as a drug or a device) such that the distinctive nature of the drug component and device component is integrated into a single product

Combination products do not include drugs and medical devices where the drug component and the device component can be used separately (for example, products sold together in procedure packages and trays).

Examples of combination products include a:

• device that carries or delivers a drug over time (for example, implant)
• device impregnated with a drug (for example, to maintain stent patency)
• drug delivery system (for example, autoinjector)
• Schedule C drug, such as radiopharmaceuticals, radiopharmaceutical kits and generators

These drug-medical device combination products are not considered kits or convenience packs under this guidance.

For more information, consult:

• Policy on drug/medical device combination products
• Radiopharmaceuticals, kits and generators: Submission information for Schedule C drugs

Policy objectives

Co-packaged drug products pose unique challenges, especially in relation to requirements for assigning DINs and for packaging and labelling. Inconsistencies in the regulatory treatment of co-packaged drug products could introduce risks to the health and safety of people in Canada.

The objectives of this guidance include:

• protecting the health and safety of people in Canada from risks arising from the sale of co-packaged drugs and medical devices
• allowing timely access to reliable and accurate consumer information about the co-packaged drug products people use
• clarifying who is responsible for maintaining post-market records and procedures, as well as post-market reporting requirements of co-packaged drug products and their components
• providing guidance on how manufacturers and third parties involved in packaging, labelling and selling co-packaged drug products can comply with the relevant legislation

Background

Health Canada addressed DIN assignment and labelling requirements for “kits” in a 1997 policy on assigning DINs for drug products in kits. Since then, we have seen a greater number and diversity of co-packaged drug products. The definitions and requirements outlined in the policy lack sufficient scope and detail to consistently address diverse types of co-packaged products.

The term “co-packaged drug products” is used to encompass the range of products that are now available. The goal is to provide clearer definitions and more detailed descriptions of regulatory requirements to ensure that all co-packaged drug products meet applicable safety, efficacy and quality standards.

Drugs must be authorized by Health Canada before being marketed in Canada. For drugs subject to the FDR, the authorization for a drug to be sold in Canada includes assigning a DIN, which must be displayed on package labels.

Drug identification numbers (DINs)

A DIN is a computer-generated 8-digit number that we assign to a drug product before it is marketed in Canada. This number uniquely identifies all drug products sold in a dosage form and is located on the label of prescription and non-prescription drugs that have been evaluated and authorized for sale in Canada.

To learn more about regulatory requirements for DINs, consult:

• Guidance document: Regulatory requirements for drug identification numbers (DINs)

For human drugs, a DIN uniquely identifies the:

• manufacturer
• brand name
• medicinal ingredient or ingredients
• strength of medicinal ingredient or ingredients
• dosage form
• route or routes of administration

A DIN:

• tells people in Canada that a drug has undergone and passed a review for the labelled indication, or indications, and complies with Canadian law
• allows consumers to search for and access information on a drug product, including the authorized conditions of use and safety information
• helps to track post-market safety activities, such as collecting adverse reaction reports, inspection reports, quality monitoring and recalling products if required

Co-packaging drugs with other products

Co-packaging drug products may introduce new risks or harm to people in Canada caused by using different products together. For example, there may be the potential for:

• drug-drug interactions
• overdosing
• adverse interactions between a drug and a medical device
• improper storage leading to the degradation of the drug or other components
• improper drug administration by a device or other component
• changes or removal of original labelling affecting the proper use of the product or the ability to trace it

The examination, authorization, labelling and post-market traceability of co-packaged drug products are critical to ensure the safety, efficacy and quality of products for consumers.

Types of co-packaged drug products: Drug kits and convenience packs

The purpose of co-packaging a drug component with other components is either:

• as an added convenience or value to the user, or
• because the components must be used together to achieve the intended effect, for example:
  • where each component contributes to a combined indication
  • where a component is added to ensure, or enhance, the effectiveness or safety of 1 or more of the components
  • to enable the administration of a drug via another specific component, such as a co-packaged drug and diluent
  • to enable the administration of concomitant-use (administered as part of a single administration event) or sequential use (administered in a sequence) drug treatment regimens

The term “co-packaged drug products” includes both drug kits and convenience packs. The authorization, packaging and labelling requirements for these types of drug products are determined by the classification of the drug components and other components packaged together, as well as their proposed use.

Drug kits

Drug kits are co-packaged drug products made up of 2 or more components, where:

• at least 1 of which is a prescription or non-prescription pharmaceutical or biologic drug subject to the FDR
• the components are used in combination to achieve a new or overarching indication and
• the drug kit or components include labelling that provides specific instructions for the use of the components together
  • for example, as part of a treatment regimen

Additional components may be included in a drug kit as a convenience to users. These components are not intended or recommended to be used in a specific combination with other components to achieve a new or overarching indication. For example, a non-specific, substitutable syringe (medical device) or alcohol swabs (NHP) can be included as convenience components to help administer an injectable drug and diluent.

Table 1: Examples of drug kits

Types of drug kits	Description and examples
Concomitant use	Several drug components or other components are co-packaged to be used together at the same time (single administration event), with an overarching indication that includes the components’ claims and directions for use in combination. Example: Paxlovid is a COVID-19 antiviral treatment that consists of 2 different drugs: nirmatrelvir and ritonavir. These 2 drugs are co-packaged together and are to be taken concurrently as part of a single therapeutic regimen.
Sequential use	Several drug components or other components are co-packaged to be used together in a specific sequence as part of a treatment regimen. Examples could include initiation or starter packs containing 1 medicinal ingredient with multiple strengths to be used in a sequence. Some components may be optional to use as part of the treatment regimen. Example: Linessa 21 and Linessa 28 oral contraceptive tablets are sold in blister packs with active pills containing sets of tablets of different strengths to be taken in a specific sequence.
Drug and diluent	A drug component co-packaged with a diluent component, used to reconstitute or dilute the drug (for example, to dissolve a drug in powder form) to prepare it for administration. Example: Herceptin is supplied as a lyophilized (freeze-dried) powder packaged with a diluent. It needs to be reconstituted with the diluent before administration.
Drug and adjuvant	Consists of a drug component co-packaged with an adjuvant used to increase the efficacy or potency of the drug component. Example: Arexvy is a suspension for injection supplied as a lyophilized antigen powder that is reconstituted with the accompanying adjuvant suspension before administration.

Convenience packs

Convenience packs bring together market-authorized therapeutic products (drug and other components, as applicable) that have individually authorized packaging and labelling. They are sold as a single unit for the convenience of the user.

The co-packaging of authorized products in a convenience pack must not:

• recommend the use of the specific constituent components in combination
• suggest a new indication or intended use that has not been previously authorized and stated on the authorized label of the individual component
• impact the intended use, safety, efficacy or quality profile of the individual components

All drug components, natural health product components and medical device components (for example, a sterile syringe) included in the convenience pack are not specific to each other and can be substituted. However, substituting components may require certain labelling changes.

Visit Table 5 for the labelling requirements for convenience packs.

All drug components and other components in a convenience pack must be authorized (where applicable) under and comply with all regulations that apply to the individual components, for example:

• prescription or non-prescription pharmaceutical and biologic drugs
• natural health products
• medical devices
• cosmetics

For example, a sterile syringe (Class II medical device) could not be added to a convenience pack if it does not have an existing Health Canada authorization.

The co-packaged product may instead meet the definition of a drug kit if:

• new claims are made for the convenience pack or
• any of the authorized labelling is removed or altered based on recommended use with other components in the convenience pack

Table 2: Examples of convenience packs

Convenience pack types	Description and examples
Administration packs	A drug component co-packaged with another component with the general intent to make it easier for users to administer the drug, though the co-packaged component is not necessarily the only item that could be used to do so. Examples: drug component co-packaged with a general-purpose measuring device, such as a measuring cup drug component co-packaged with an authorized non-specific, substitutable, sterile syringe Note: In some cases, a co-packaged drug and delivery or administration device may be classified as a drug-medical device combination product (DDCP) and not as an administration pack. A sponsor may submit a classification request to Health Canada as per the policy on DDCPs.
Value packs	Co-packaged products that offer value incentives for users by providing a variety of products or quantities of items in a single package. Examples: 2 co-packaged medicated shampoo bottles back-to-school value pack containing deodorant, hand cream, lip balm and non-prescription pain relief tablets seasonal value packs, such as assorted sunscreen products in a summer value pack

Establishment and site licensing requirements

Activities such as packaging, labelling, importing and distributing pre-packaged drugs in a secondary package could require an establishment (drug) or site licence (natural health product), or both. The activities of importing or distributing medical devices of all classes require a medical device establishment licence (MDEL). The need to hold an MDEL is subject to certain exemptions (outlined in GUI-0016). Depending on the types of components in a co-packaged drug product, several types of establishment or site licences may be required.

For more information, consult:

• For prescription and non-prescription pharmaceutical and biologic drugs: Guidance on drug establishment licences (GUI-0002)
• For medical devices: Guidance on medical device establishment licensing (GUI-0016)
• For natural health products: Site licensing guidance document

Companies that package, label, import or distribute therapeutic products should ensure they are properly licensed to conduct those activities.

Companies that import therapeutic products must ensure they meet import requirements for any therapeutic products they are importing that will be subsequently co-packaged or sold.

For more information, consult:

• Importing and exporting health products for commercial use (GUI-0117)

Post-market reporting requirements

Regulated parties must understand and comply with applicable post-market reporting obligations. In some cases, additional post-market requirements may be imposed as terms and conditions to help ensure the continued safety and effectiveness of a product.

Serious adverse reactions and medical device incidents

Manufacturers and hospitals must report serious harm involving the co-packaged drug product to Health Canada within established timelines. This also applies to importers of medical devices. This includes any serious adverse reactions (ARs) or medical device incidents (MDIs) related to any drug, natural health product or medical device component that could impact patient safety.

Other observations subject to reporting include:

• abuse
• misuse
• overdose
• medication incidents
• occupational exposure
• unusual failure in efficacy for new drugs
• use errors that result or potentially result in serious deterioration in health or death

On occasion, you may need to submit 2 reports to Health Canada for the same serious AR or MDI related to a drug kit:

• 1 for the drug kit and
• 1 for the drug or other component (natural health product or medical device) of the drug kit

For example, a serious AR related to a drug component of a drug kit that’s also marketed as an individual drug must be reported for the drug kit and the individual drug product.

For more information, consult:

• Incident reporting for medical devices: Guidance document
• Reporting adverse reactions to marketed health products: Guidance document for industry

Summary reporting

Summary reports for drug kits must be prepared in accordance with the regulatory requirements outlined in the FDR. As applicable, Health Canada may also request:

• an issue analysis of safety and effectiveness for the medical device sold in a co-packaged product
• an interim summary report for the natural health product (NHP) sold in a co-packaged product

For more information, consult:

• Guidance on summary reports and issue-related analyses for medical devices: Summary reports
• Preparing and submitting summary reports for marketed drugs and natural health products: Guidance document for industry

Post-market safety and recalls

Regulated parties that market drugs, natural health products and medical devices play an important role in ensuring the safety and effectiveness of any product they sell, manufacture or import in Canada.

When a drug component or other component in a co-packaged drug product is recalled, the entire drug kit or convenience pack may have to be recalled. For example, if a component is found to be defective or unsafe, the entire drug kit may be recalled to ensure user safety.

Regulated parties are responsible for meeting all post-market safety monitoring and reporting requirements for their co-packaged products. They must also ensure that recalls of co-packaged products and components are conducted effectively and quickly.

Importers and distributors must:

• maintain records and procedures that help identify post-market risks (for example, through complaints)
• ensure product traceability (for example, distribution records) and
• be able to perform a rapid and effective recall, if needed (for example, recall procedure)

Agreements with other parties in the supply chain, such as other manufacturers, wholesalers, assemblers, distributors or storage sites, should clearly define their individual responsibilities during a recall.

For more information on recalls, consult:

• Drug, natural health product and biocide recall guide (GUI-0039)
• Guide to recall of medical devices (GUI-0054)

Note about guidance documents in general

Guidance documents provide assistance to industry and health care providers on how to comply with governing statutes and regulations. They also provide guidance to Health Canada staff on how mandates and objectives should be met fairly, consistently and effectively.

Guidance documents are administrative, not legal, instruments. This means that flexibility can be applied. However, to be acceptable, alternate approaches to the principles and practices described in this document must be supported by adequate justification. They should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As always, Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, to help us adequately assess the safety, efficacy or quality of a therapeutic product. We are committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read along with the relevant sections of the regulations and other applicable guidance documents.